Integrase Inhibitor and Metformin Pharmacological Interactions: Implications for Glycemic Control in Type 2 Diabetes Mellitus Patients with HIV Infection

Arionget Jemima

Department of Pharmacoepidemeology Kampala International University Uganda

Email: jemima.arionget@studwc.kiu.ac.ug

ABSTRACT

Integrase strand transfer inhibitors (INSTIs) represented the preferred first-line antiretroviral therapy for HIV infection due to superior virological efficacy and tolerability profiles. However, emerging evidence suggested that certain INSTIs, particularly dolutegravir and bolutegravir, may adversely affect glucose metabolism and interfere with metformin pharmacokinetics through inhibition of organic cation transporters. Metformin remains the cornerstone treatment for type 2 diabetes mellitus, with over 40 percent of HIV-infected individuals developing metabolic complications including diabetes. This review critically evaluated the pharmacological interactions between integrase inhibitors and metformin, examining mechanisms of drug-drug interactions, effects on glycemic control, clinical outcomes, and management strategies in patients with concurrent type 2 diabetes and HIV infection. A comprehensive literature search of PubMed, EMBASE, Cochrane Library, and clinical trial registries was conducted for peer-reviewed studies published between 2013 and 2025 examining INSTI-metformin interactions and glycemic outcomes. Dolutegravir significantly inhibited renal organic cation transporter-2 and multidrug and toxin extrusion proteins, reducing metformin renal clearance by 30-40 percent and increasing plasma concentrations by similar magnitudes. This pharmacokinetic interaction correlated with enhanced metformin-related adverse effects, including gastrointestinal symptoms and lactic acidosis risk but paradoxically may improve glycemic control in some patients. Clinical studies demonstrated heterogeneous glycemic outcomes, with some investigations reporting improved HbA1c reductions while others document attenuated metformin efficacy attributed to INSTI-induced insulin resistance. Bictegravir and cabotegravir exhibit minimal transporter inhibition and reduced interaction potential. INSTI-metformin interactions presented complex clinical implications requiring individualized management approaches, dose adjustments, and enhanced monitoring to optimize both HIV virological control and glycemic management while minimizing adverse effects.

Keywords: Integrase inhibitors, Metformin, Drug interactions, Type 2 diabetes mellitus, HIV infection

CITE AS: Arionget Jemima (2026). Integrase Inhibitor and Metformin Pharmacological Interactions: Implications for Glycemic Control in Type 2 Diabetes Mellitus Patients with HIV Infection. RESEARCH INVENTION JOURNAL OF SCIENTIFIC AND EXPERIMENTAL SCIENCES 6(1):13-20. https://doi.org/10.59298/RIJSES/2026/611320